Acute Kidney Injury: Staging, Causes and Immediate Management

Introduction

Acute kidney injury is an abrupt deterioration in renal function over hours to days, resulting in the retention of nitrogenous waste, dysregulation of fluid and electrolyte balance, and impaired acid-base homeostasis.¹ The older term 'acute renal failure' has been abandoned deliberately, because it implied a binary event, whereas even modest rises in creatinine carry prognostic significance.

AKI is remarkably common and is detected in around 15 to 20% of hospital admissions, rising far higher in critical care.² It matters for three reasons: it is associated with a substantial increase in inpatient mortality; a significant proportion of cases are avoidable, arising from dehydration, sepsis and nephrotoxic prescribing; and even apparently full biochemical recovery leaves an increased long-term risk of chronic kidney disease.

Definition and staging

The KDIGO criteria are the internationally accepted definition and are used by the automated e-alert systems now embedded in UK laboratory reporting.¹ AKI is present if any one of the following is met:

• A rise in serum creatinine of 26 micromol/L or more within 48 hours
• A rise in serum creatinine to 1.5 times the baseline or more, known or presumed to have occurred within the preceding 7 days
• A urine output of less than 0.5 mL/kg/hour for more than 6 consecutive hours

Causes

Classifying by anatomical site is the most useful bedside approach, because each category has a distinct investigation and management pathway. In practice the categories frequently overlap - prolonged pre-renal hypoperfusion progresses to intrinsic acute tubular necrosis if uncorrected.

Pre-renal (reduced renal perfusion)

The commonest category, accounting for the majority of hospital-acquired AKI. The renal parenchyma is initially structurally normal and function recovers rapidly if perfusion is restored - which is what makes early recognition so valuable.

Intrinsic renal

Post-renal (obstruction)

Obstruction is the category most important not to miss, because it is often rapidly and completely reversible with a catheter or a nephrostomy - and because prolonged obstruction causes permanent damage. Bear in mind that obstruction must be bilateral (or unilateral in a single functioning kidney) to raise the creatinine.

• Bladder outlet obstruction - benign prostatic hyperplasia (much the commonest cause overall), prostate cancer, urethral stricture, and the frequently forgotten blocked urinary catheter
• Ureteric obstruction - bilateral calculi, pelvic or retroperitoneal malignancy, retroperitoneal fibrosis, ureteric stricture, iatrogenic ligation during pelvic surgery
• Intraluminal - clot, sloughed papillae, or a stone at the pelviureteric junction
• Neurogenic bladder - spinal cord pathology, diabetic autonomic neuropathy, and anticholinergic drugs causing acute retention

Risk factors

NICE recommends actively identifying patients at risk, because prevention is far more effective than treatment.²

• Age 65 or over
• Pre-existing chronic kidney disease - the single strongest risk factor; an eGFR under 60 markedly increases susceptibility
• Heart failure, liver disease and diabetes mellitus
• Sepsis and hypovolaemia of any cause
• Nephrotoxic drugs - NSAIDs, ACE inhibitors and ARBs, diuretics, aminoglycosides, calcineurin inhibitors
• Iodinated contrast within the past week
• Recent major surgery, particularly cardiac and vascular surgery, and emergency laparotomy
• Symptoms or history of urological obstruction
• Previous AKI
• Cognitive impairment or dependence for fluid intake, which predisposes to unrecognised dehydration

Clinical features

Most AKI is detected biochemically before it becomes symptomatic, often through an automated e-alert.⁴ When features are present they arise either from the underlying cause, from fluid and electrolyte disturbance, or from uraemia.

• Oliguria or anuria - though a substantial proportion of AKI is non-oliguric, so normal urine output is reassuring only in part
• Features of the cause - thirst, postural dizziness and reduced skin turgor in hypovolaemia; fever and rigors in sepsis; loin pain and haematuria in stones; a palpable bladder and poor stream in obstruction; rash and arthralgia in vasculitis
• Fluid overload - peripheral and pulmonary oedema, raised JVP, orthopnoea and hypoxia, particularly once oliguria is established or fluids have been given liberally
• Uraemic features - anorexia, nausea and vomiting, fatigue, pruritus, hiccups, restless legs, confusion and, at the severe end, asterixis, seizures, uraemic encephalopathy and a pericardial rub from uraemic pericarditis
• Hyperkalaemic features - usually silent, but may cause muscle weakness, paraesthesiae or palpitations, and can present as cardiac arrest
• Kussmaul (deep, sighing) respiration in severe metabolic acidosis

Investigations

Bedside

• Urine dipstick, in every patient, before catheterisation where possible - this is the single most discriminating bedside test. Blood and protein together suggest intrinsic glomerular disease and should prompt urgent nephrology discussion; a bland dipstick favours a pre-renal or post-renal cause. Leucocytes and nitrites suggest infection.
• Urine microscopy - muddy brown granular casts in ATN, red cell casts and dysmorphic red cells in glomerulonephritis, white cell casts in interstitial nephritis or pyelonephritis, crystals in tumour lysis or ethylene glycol
• ECG - to look for the changes of hyperkalaemia (tented T waves, small or absent P waves, broad QRS, and ultimately a sine wave pattern)
• Fluid balance chart, daily weights and observations
• Bladder scan - for residual volume, to identify retention

Laboratory

• U&Es - creatinine, urea and potassium; compare against every available previous result to establish a baseline and the rate of change
• Venous blood gas or bicarbonate - for metabolic acidosis, and a rapid potassium in the unstable patient
• Full blood count and CRP - anaemia may suggest CKD or myeloma; thrombocytopenia raises thrombotic microangiopathy; eosinophilia suggests interstitial nephritis
• Bone profile - hypercalcaemia suggests myeloma or malignancy; hyperphosphataemia and hyperkalaemia with a high urate suggest tumour lysis
• Creatine kinase - if there is any suggestion of a fall, immobility, seizure, compartment syndrome or statin use, to detect rhabdomyolysis
• Blood cultures and a septic screen where infection is possible
• Liver function and clotting
• Immunology and myeloma screen, where intrinsic renal disease is suspected - ANA, ANCA, anti-GBM antibodies, complement C3 and C4, immunoglobulins, serum free light chains and serum/urine electrophoresis, plus ASOT and hepatitis and HIV serology as indicated

Imaging

• Renal tract ultrasound within 24 hours is recommended if obstruction is suspected, if there is no identified cause, or if the patient is not improving as expected. It looks for hydronephrosis, kidney size and echogenicity (small echogenic kidneys indicate CKD), and stones or masses.²
• Ultrasound within 6 hours if pyonephrosis (an obstructed, infected kidney) is suspected - fever and loin pain with obstruction is a urological emergency needing immediate decompression
• Ultrasound is not always needed where the cause is clearly pre-renal and the patient responds promptly to treatment
• CT for suspected retroperitoneal pathology, malignancy or stone disease where ultrasound is inconclusive - avoid contrast where possible
• Renal biopsy - reserved for suspected intrinsic renal disease of uncertain cause, particularly rapidly progressive glomerulonephritis, where the result will change treatment

Management

There is no specific drug that reverses AKI. Management is supportive and directed at the cause: restore perfusion, remove the insult, relieve obstruction, and treat complications while the kidney recovers.

Treat the cause and restore perfusion

• Hypovolaemia - give intravenous crystalloid (a balanced solution such as Hartmann's, or 0.9% sodium chloride), titrated in boluses with reassessment of fluid status after each. Aim to restore euvolaemia, not to force a diuresis. Beware of over-filling the oliguric patient.
• Sepsis - treat per the sepsis pathway with prompt antibiotics and source control; renal recovery follows haemodynamic recovery
• Cardiogenic causes - fluids will worsen matters; the priority is improving cardiac output, and diuresis may be needed despite the AKI
• Obstruction - catheterise for bladder outlet obstruction (and flush or replace an existing catheter that may be blocked), and involve urology for nephrostomy or ureteric stenting in upper tract obstruction
• Intrinsic disease - discuss urgently with nephrology; immunosuppression (corticosteroids, cyclophosphamide, rituximab, plasma exchange) may be needed for vasculitis or anti-GBM disease, and delay costs nephrons

Treat the complications

Renal replacement therapy

Escalation and follow-up

• Discuss with nephrology where there is stage 3 AKI, suspected intrinsic renal disease (especially a positive dipstick for blood and protein), an unclear cause, failure to improve, or a possible indication for RRT²
• Involve urology urgently for obstruction requiring decompression
• Monitor U&Es at least daily while AKI is evolving, along with fluid balance and weight
• On recovery, review and restart held medications deliberately - ACE inhibitors and other drugs are frequently omitted permanently by accident, or restarted too early; document a clear plan
• Arrange follow-up renal function after discharge, since AKI confers an increased long-term risk of CKD, and check for persistent proteinuria
• Document the episode clearly in the discharge summary, including the cause, the drugs stopped and whether they should be restarted

Complications

• Hyperkalaemia with arrhythmia and cardiac arrest
• Pulmonary oedema from fluid overload, often iatrogenic
• Metabolic acidosis
• Uraemic complications - encephalopathy, seizures, pericarditis and pericardial effusion, platelet dysfunction with bleeding
• Hyperphosphataemia and hypocalcaemia
• Increased susceptibility to infection, and to the toxicity of drugs that are renally cleared
• Progression to chronic kidney disease - a well-established association even after apparent recovery, and the reason follow-up matters
• End-stage renal disease requiring long-term dialysis in a minority
• Substantially increased short- and long-term mortality, and increased subsequent cardiovascular risk

Red flags

Prognosis

Outcome depends principally on the cause, the stage and the comorbidity of the patient rather than on the creatinine itself. Pre-renal AKI recognised and corrected early usually recovers completely within days. Established ATN typically recovers over 1 to 3 weeks, often passing through a polyuric recovery phase as tubular function returns before concentrating ability does - a phase during which fluid and electrolyte losses can be substantial and need replacing.

AKI nonetheless carries a substantial excess inpatient mortality, reaching well above 30 to 40% in patients with stage 3 AKI in critical care. Much of this reflects the severity of the underlying illness - sepsis, cardiac failure, major surgery - rather than the renal failure alone, but AKI is an independent contributor.

The most under-appreciated point is what happens afterwards. An episode of AKI, even one that appears to resolve fully, is associated with a significantly increased long-term risk of chronic kidney disease, end-stage renal disease, cardiovascular events and death.³ A proportion of patients never return to their true baseline. This is why every patient needs their renal function and proteinuria rechecked after discharge, their medication restarted deliberately rather than by default, and the episode documented so that future prescribers know they are dealing with a susceptible kidney.